Emil fischer



NITED STATES T FFIGEe EMIL FISCHER, OF BERLIN, GERMANY, ASSIGN OR TO C.F. BOEHRINGER &

SOEHNE, OF VVALDI-IOF, GERMANY.

BROMOTHEOPHYL LIN AND PROCESS OF MAKING SAME.

SPECIFICATION forming part of Letters Patent No. 571,353, dated November17, 1896. Application filed September 23, 1895. Serial No. 568,428.(Specimens) To all lull/omit may concern.-

Be it known that I, EMIL FISCHER, a citizen of Germany, residing atBerlin, Germany, have invented a certain new and useful Com- 5pound,Bromotheophyllin,and Process of Preparing the Same; and I dohereby declare the following to be a full, clear, and exact descriptionof the invention, such as will enable others skilled in the art to whichit ap- 1o pertains to make and use the same.

This invention relates to the manufacture of derivatives of theophyllinand it consists in the new compound, bromotheophyllin, and the processof obtaining the same, all as will I 5 be hereinafter set forth, andmore particularly pointed out in the claims.

I have found, as the result of experiments, that a compound which Iterm, bromotheophyllin, and which has the formula H may be obtained byheating theophyllin to gether with bromin under pressure.

The following is the preferred method in which I propose to carry myinvention into practice: One part of finely-powdered theophyllin, whichhas been dried at 110 centigrade, is heated with five parts bromin to100 centigrade and retained at that tempera- 3 5 ture for several hoursin a tightly-closed vessel. Thereupon, to remove the excess of bromin,the vessel is opened and the tem perature of the contents is raised to150 centigrade and held there until the evolution and escape of freebromin has ceased. The residue is then triturated or otherwisecomminuted and then treated wit-h aqueous sulfurous acid in excess andgently heated, for the purpose of completely discolorizing the same. Thecrude bromotheophyllin so obtained is then completely purified bydissolving it in lye, such as soda-lye, and treatedwith animal charcoal.Thereupon the product is precipi tated out of the lye-bath by acid, andthe precipitate is then recrystallized with alcohol. 'This bro1noderivative of theophyllin p0s-= sesses certain valuable properties, viz:The physiological action of it on the organism is the same as that ofcaffein and theobromin. Doses 0.5 to 1.5 grains.

Bromotheophyllin is soluble with some difficulty in warm alcohol, andfrom such solutions it crystallizes in small, thin, colorless,spear-shaped crystals, which melt at a temperature which is not quiteconstant and which is between 315 and 320 centigrade. In melting theyare colored brown and completely decomposed.

In water the bromotheophyllin is soluble with great difficulty, even ata high'heat. It is readily taken up in dilute alkalies, includingammonia, while strong alkalies precipitate its alkali salts from itsaqueous solution in crystalline form.

The silver salt of bromotheophyllin is precipitated from an ammoniacalsolution of the same.

By the addition of silver nitrate to an ammoniacal solution of thebromotheophyllin the silver salt of the same is precipitated first 7 5as an amorphous colorless precipitate, which becomes granular, however,on boiling. This silver salt is soluble in much ammonia, and uponevaporating the ammonia by boiling it separates in the form of acolorless crystalline precipitate consisting of very small needles. Itsformula, as above stated, is:

oI-nN-onr I ll co G-NII on,n-c=n WVhat I claim, and desire to secure byLetters Patent, is-- 1. The process which consists in mixing theophyllinwith bromin, and then heating 'the mixture, substantially as set forth.

2. The process which consists in mixing 5 theophyllin with bromin, andthen heating the mixture under pressure, substantially as set forth.

3. The process which consists in mixing theophyllin with bromin in theproportion of one part of the former to five parts of the latter, thenheating the mixture to cen- IOO.

tigrade, and retaining the same at this temperature in a closed vessel,substantially as set forth.

4. The process which consists in the following steps: first, mixingtheophyllin and bromin in the proportion of one part of the former tofive parts of the latter, then heating the mixture in a closed vessel to100 centigrade, and retaining it at that temperature for several hours,then opening the vessel and raising the temperature to about 150centigrade, to drive off the excess of bromin, substantially as setforth.

5. The process which consists in mixing theophyllin with bromin, thenheating the mixture under pressure, and then driving off the excess ofbromin and purifying the residue, substantially as set forth.

0. The process which consists in the following steps: first, mixingtheophyllin and bromin in the proportion of one part of the former tofive parts of the latter, then heating the mixture in a closed vessel to100 centigrade, and retaining it at that temperature for several hours,then opening the vessel and raising the temperature to about 150centigrade, to drive off the excess of bromin,

and then purifying the residue, substantially as set forth.

7 The process which consists in mixing theophyllin with bromin in theproportion of one part of the former to five parts of the latter, thenheating the mixture to 100 centigrade, and retaining the same at thistemperature in a closed vessel, then driving off the excess of bromin,then decolorizing the residue, then dissolving the crudebromotheophyllin obtained in lye and treating with animal charcoal, andfinally precipitating it by acid and recrystallizing the precipitatefrom alcohol, substantially as set forth.

8. As a new compound, bromotheophyllin havin gthe formula hereinbeforestated,whose melting-point is between 315 and 320 centigrade, which issoluble with difficulty in alcohol and water, but readily taken up bydilute alkalies.

In testimony whereof I affix my signature in presence of two witnesses.

EMIL FISCHER. \Vitnesses:

OSCAR GUNNERLING, P. REHLANDER.

